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Efficacies of calcium-EDTA in combination with imipenem in a murine model of sepsis caused by Escherichia coli with NDM-1 β-lactamase.

Abstract
We evaluated the efficacy of ethylenediamine-N,N,N',N'-tetraacetic acid, disodium calcium salt (Ca-EDTA), as an inhibitor for New Delhi metallo-β-lactamase-1 (NDM-1) in vitro antibiotic susceptibility and in a mouse model of sepsis caused by Escherichia coli. Ca-EDTA drastically reduced the MICs of carbapenems for all NDM-producing bacteria [imipenem (IPM) ≤1-2 μg/ml; meropenem (MEPM) ≤1-4 µg/ml]. In the neutropenic murine model of sepsis, the bacterial burden was further reduced by combination therapy using imipenem/cilastatin sodium (IPM/CS) and Ca-EDTA to 2.3 × 10(3) CFU/liver, compared with 2.9 × 10(4) CFU/liver for IPM/CS alone. These data demonstrated the possibility of Ca-EDTA for clinical applications. In our understanding, this is the first report examining the effect of Ca-EDTA on a mouse sepsis model caused by NDM-1-producing bacteria.
AuthorsAyumi Yoshizumi, Yoshikazu Ishii, David M Livermore, Neil Woodford, Soichiro Kimura, Tomoo Saga, Sohei Harada, Keizo Yamaguchi, Kazuhiro Tateda
JournalJournal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (J Infect Chemother) Vol. 19 Issue 5 Pg. 992-5 (Oct 2013) ISSN: 1437-7780 [Electronic] Netherlands
PMID23233082 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Imipenem
  • Edetic Acid
  • beta-Lactamases
  • beta-lactamase NDM-1
Topics
  • Animals
  • Anti-Bacterial Agents (pharmacology, therapeutic use)
  • Bacterial Load (drug effects)
  • Colony Count, Microbial
  • Disease Models, Animal
  • Edetic Acid (pharmacology)
  • Escherichia coli (drug effects, enzymology)
  • Escherichia coli Infections (drug therapy, microbiology)
  • Imipenem (pharmacology)
  • Mice
  • Microbial Sensitivity Tests
  • Sepsis (drug therapy, microbiology)
  • beta-Lactam Resistance
  • beta-Lactamases (biosynthesis)

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